Project Summary/Abstract Migraine headaches represent the third most prevalent medical disorder on the planet, yet many sufferers are not satisfactorily treated, and 3% of them suffer chronification of their migraine every year. Cortical spreading depression and hyperexcitability of the brain have been demonstrated in migraine, and migraine pain has been related to neuroinflammation. In this project, we propose to use PET/MRI using a translocator protein marker (TSPO), as well as a measure of the infra-slow oscillatory activity to assess neuroinflammation in migraine. Then, we will examine the effect of a mind-body therapy on neuroinflammation. Our design will combine a top- down approach, namely mindfulness mediation, with a bottom-up approach, i.e. non-invasive transcutaneous vagus nerve stimulation, and examine the synergistic effect of these therapies on both microglial/astrocytic activation as measured with PET and on the fluctuation of low-frequency oscillatory activity. Our results will indicate whether a coupling of a top-down with a bottom-up therapeutic approach can have measurable effects on neuroinflammation in migraine, and indicate whether glial activation may be a therapeutic target for migraine.